OBJECTIVE: The purpose of this study was to identify histologic characteristics of advanced coronary atherosclerotic plaques that are related with the detection of the napkin-ring sign (NRS) in coronary CT angiography (CCTA). METHODS: CCTA was performed in 7 human donor hearts. Histological slicing and stainings were performed in 1 mm increments of each major coronary artery. Histology was co-registered with the CT-data and classified according to the modified AHA classification. RESULTS: Advanced plaques (types IV-VI) were present in 139 (23%) of 611 cross sections. Of these 33 (24%) demonstrated an NRS in CCTA. NRS plaques were associated with greater non-core plaque area (median 10.2 vs. 6.4 mm(2), p < 0.01) and larger vessel area (median 17.1 vs. 13.0 mm(2), p < 0.01). The area of the necrotic/lipid core was larger in plaques with NRS (median 1.1 vs. 0.5 mm(2), p = 0.05). Angiogenesis tended to be more frequent in plaques with NRS (48% vs. 30%) whereas micro-calcifications tended to be more frequent in plaques without NRS (27% vs. 46%) (p = 0.06 and 0.07 respectively). In a multivariate analysis, necrotic/lipid core area (OR = 1.9), non-core plaque area (OR = 1.6), and total vessel area (OR = 0.9) independently predicted the appearance of the NRS in coronary CT angiography. CONCLUSION: Delineation of NRS in CCTA is independently linked to the size of the necrotic/lipid core, the size of the non-core plaque and to the vessel area as measured in histology of advanced coronary atherosclerotic plaques.